Highest mortality rate (non-inherited disease)
transmissible spongiform encephalopathies
100 percentage
Not Applicable ()

The disease with the highest known case fatality rate is group of exceptionally rare brain diseases called prion diseases or transmissible spongiform encephalopathies (TSEs). These are spread by the ingestion of abnormal proteins called prions. Prions are misfolded malfunctioning versions of common proteins that have the ability to transmit their shape to the normal versions of the same protein.

Examples of these prion diseases include variant Creutzfeldt-Jakob Disease (vCJD), which is thought to be caused by the ingestion of prions from cows with an animal form of TSE; and Kuru, a disease recorded only in a small population of practising cannibals in Papua New Guinea in the 1950s. There are a few other forms of prion disease that are either genetically heritable or caused by seemingly random mutation.

Prion diseases are incredibly rare. The most common, non-transmissible, form is classical Creutzfeldt-Jakob Disease, which has a prevalence of around 1 in 1 million. There are no known treatments for prion diseases, which cause the degeneration of brain tissue and result in death within 4–14 months.

In addition to these extremely rare diseases, there are also a number of more common infections that have a case fatality rate close enough to 100% for the difference to be statistically insignificant.

The most common of these deadly infections is rabies, a virus that causes around 17,000 deaths a year. Rabies can be effectively prevented by post-exposure prophylaxis (PEP; the administration of a vaccine after infection) but it is not treatable once the patient has begun to show symptoms. As of 2016, a total of 14 people are known to have survived symptomatic rabies infection.